Variant chr1-171638562-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000261.2(MYOC):c.730+35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 1,611,202 control chromosomes in the GnomAD database, including 422,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 44199 hom., cov: 31)

Exomes 𝑓: 0.72 ( 378034 hom. )

Consequence

MYOC
NM_000261.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -5.89

Variant links:

Genes affected

MYOC (HGNC:7610): (myocilin) MYOC encodes the protein myocilin, which is believed to have a role in cytoskeletal function. MYOC is expressed in many occular tissues, including the trabecular meshwork, and was revealed to be the trabecular meshwork glucocorticoid-inducible response protein (TIGR). The trabecular meshwork is a specialized eye tissue essential in regulating intraocular pressure, and mutations in MYOC have been identified as the cause of hereditary juvenile-onset open-angle glaucoma. [provided by RefSeq, Jul 2008]

MYOC links:

MYOCOS (HGNC:53429): (myocilin opposite strand)

MYOCOS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 1-171638562-C-T is Benign according to our data. Variant chr1-171638562-C-T is described in ClinVar as [Benign]. Clinvar id is 1259809.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOC	NM_000261.2 linkuse as main transcript	c.730+35G>A		intron_variant		ENST00000037502.11	NP_000252.1	Q99972A0A0S2Z421

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MYOC	ENST00000037502.11 linkuse as main transcript	c.730+35G>A	intron_variant	1	NM_000261.2	ENSP00000037502.5	Q99972
MYOCOS	ENST00000637303.1 linkuse as main transcript	c.235-68C>T	intron_variant	5		ENSP00000490048.1	A0A1B0GUC4
MYOC	ENST00000638471.1 linkuse as main transcript	n.*68+35G>A	intron_variant	5		ENSP00000491206.1	A0A1W2PP09

Frequencies

GnomAD3 genomes

AF:

0.759

AC:

115307

AN:

152002

Hom.:

44146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.866

Gnomad AMI

AF:

0.692

Gnomad AMR

AF:

0.700

Gnomad ASJ

AF:

0.790

Gnomad EAS

AF:

0.773

Gnomad SAS

AF:

0.805

Gnomad FIN

AF:

0.718

Gnomad MID

AF:

0.845

Gnomad NFE

AF:

0.707

Gnomad OTH

AF:

0.763

GnomAD3 exomes

AF:

0.722

AC:

181475

AN:

251352

Hom.:

66284

AF XY:

0.728

AC XY:

98893

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.861

Gnomad AMR exome

AF:

0.597

Gnomad ASJ exome

AF:

0.795

Gnomad EAS exome

AF:

0.771

Gnomad SAS exome

AF:

0.813

Gnomad FIN exome

AF:

0.702

Gnomad NFE exome

AF:

0.705

Gnomad OTH exome

AF:

0.727

GnomAD4 exome

AF:

0.718

AC:

1047906

AN:

1459082

Hom.:

378034

Cov.:

AF XY:

0.722

AC XY:

523823

AN XY:

725936

show subpopulations

Gnomad4 AFR exome

AF:

0.867

Gnomad4 AMR exome

AF:

0.608

Gnomad4 ASJ exome

AF:

0.789

Gnomad4 EAS exome

AF:

0.795

Gnomad4 SAS exome

AF:

0.813

Gnomad4 FIN exome

AF:

0.704

Gnomad4 NFE exome

AF:

0.706

Gnomad4 OTH exome

AF:

0.736

GnomAD4 genome

AF:

0.759

AC:

115416

AN:

152120

Hom.:

44199

Cov.:

AF XY:

0.760

AC XY:

56535

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.866

Gnomad4 AMR

AF:

0.699

Gnomad4 ASJ

AF:

0.790

Gnomad4 EAS

AF:

0.773

Gnomad4 SAS

AF:

0.806

Gnomad4 FIN

AF:

0.718

Gnomad4 NFE

AF:

0.707

Gnomad4 OTH

AF:

0.761

Alfa

AF:

0.722

Hom.:

50031

Bravo

AF:

0.755

Asia WGS

AF:

0.785

AC:

2732

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 28792703, 16863615) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.015

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over